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Magnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42-5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants' pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.

Objective To quantify the impact and accuracy of different screening approaches for cervical cancer, including liquid based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and their combinations via parallel co-testing and sequential triage. The secondary goal was to predict the effect of differing coverage rates of HPV vaccination on the performance of screening tests and in the interpretation of their results. Design Modelling study. Main outcomes measured Different screening modalities were compared in terms of number of cases of Cervical intra-epithelial neoplasia (CIN) grade 2 and 3 detected and missed, as well as the number of false positives leading to excess colposcopy, and number of tests required to achieve a given level of accuracy. The positive predictive value (PPV) and negative predictive value (NPV) of different modalities were simulated under varying levels of HPV vaccination. Results The model predicted that in a typical population, primary LBC screening misses 4.9 (95% Confidence Interval (CI) 3.5-CIN 2 / 3 cases per 1000 women, and results in 95 (95% CI: 93-97%) false positives leading to excess colposcopy. For primary HPV testing, 2.0 (95% CI: 1.9-2.1) cases were missed per 1000 women, with 99 (95% CI: 98-101) excess colposcopies undertaken. Co-testing markedly reduced missed cases to 0.5 (95% CI: 0.3-0.7) per 1000 women, but at the cost of dramatically increasing excess colposcopy referral to 184 per 1000 women (95% CI: 182-188). Conversely, triage testing with reflex screening substantially reduced excess colposcopy to 9.6 cases per 1000 women (95% CI: 9.3 - 10) but at the cost of missing more cases (6.4 per 1000 women, 95% CI: 5.1 - 8.0). Over a life-time of screening, women who always attend annual and 3-year co-testing were predicted to have a virtually 100% chance of falsely detecting a CIN 2 / 3 case, while 5 year co-testing has a 93.8% chance of a false positive over screening life-time. For annual, 3 year, and 5 year triage testing (either LBC with HPV reflex or vice versa), lifetime risk of a false positive is 35.1%, 13.4%, and 8.3% respectively. HPV vaccination rates adversely impact the PPV, while increasing the NPV of various screening modalities. Results of this work indicate that as HPV vaccination rates increase, HPV based screening approaches result in fewer unnecessary colposcopies than LBC approaches. Conclusion The clinical relevance of cervical cancer screening is crucially dependent upon the prevalence of cervical dysplasia and/or HPV infection or vaccination in a given population, as well as the sensitivity and specificity of various modalities. Although screening is life-saving, false negatives and positives will occur, and over-testing may cause significant harm, including potential over-treatment.

Key Points Question As human papillomavirus (HPV)–based cervical screening modalities change and HPV vaccination becomes more widespread, what are the likely outcomes for the interpretation of screening modalities? Findings In this decision analytical model with a simulated population of women aged 25 years and older, HPV-based screening modalities detected more abnormal cervical cells than traditional liquid-based cytology (LBC) approaches, but they did so at the cost of increased false positives. However, as HPV vaccination increased, HPV-based modalities resulted in fewer unnecessary colposcopies than LBC methods. Meaning These findings suggest that the ideal screening modality for a given population should account for HPV vaccination status to maximize the efficiency of screening., This decision analytical model estimates the likely outcomes of different screening modalities and models the effect of growing uptake of the human papillomavirus (HPV) vaccine on the interpretation of screening results., Importance Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. Objectives To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. Design, Setting, and Participants This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged ≥25 years), considering different levels of HPV vaccination. Main Outcomes and Measures The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. Results In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies). Conclusions and Relevance In this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.

Editor – Weir and colleagues timidly state that ‘If vitamin D does in fact reduce the severity of COVID-19 … [then] supplements would offer a relatively easy option to decrease the impact of the pandemic.’[1][1] This reticence ignores about 40 years of developing scientific knowledge of the

ObjectivesDisinformation on medical matters has become an increasing public health concern. Public engagement by scientists, clinicians and patient advocates can contribute towards public understanding of medicine. However, depth of feeling on many issues (notably vaccination and cancer) can lead to adverse reactions for those communicating medical science, including vexatious interactions and targeted campaigns. Our objective in this work is to establish a taxonomy of common negative experiences encountered by those communicating medical science, and suggest guidelines so that they may be circumvented.DesignWe establish a taxonomy of the common negative experiences reported by those communicating medical science, informed by surveying medical science communicators with public platforms.Participants142 prominent medical science communicators (defined as having >1000 Twitter followers and experience communicating medical science on social and traditional media platforms) were invited to take part in a survey, with 101 responses.Results101 responses were analysed. Most participants experienced abusive behaviour (91.9%), including persistent harassment (69.3%) and physical violence and intimidation (5.9%). A substantial number (38.6%) received vexatious complaints to their employers, professional bodies or legal intimidation. The majority (62.4%) reported negative mental health sequelae due to public outreach, including depression, anxiety and stress. A significant minority (19.8%) were obligated to seek police advice or legal counsel due to actions associated with their outreach work. While the majority targeted with vexatious complaints felt supported by their employer/professional body, 32.4% reported neutral, poor or non-existent support.ConclusionsThose engaging in public outreach of medical science are vulnerable to negative repercussions, and we suggest guidelines for professional bodies and organisations to remedy some of these impacts on front-line members.

Objective: We conducted a systematic review of the literature on the effectiveness of medical abortion “reversal” treatment. Since the usual care for women seeking to continue pregnancies after ingesting mifepristone is expectant management with fetal surveillance, we also performed a systematic review of continuing pregnancy after mifepristone alone. Study design: We searched PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus and the Cochrane Library for articles published through March 2015 reporting the proportion of pregnancies continuing after treatment with either mifepristone alone or after an additional treatment following mifepristone aimed at reversing its effect. Results: From 1115 articles retrieved, 1 study met inclusion criteria for abortion reversal, and 13 studies met criteria for continuing pregnancy after mifepristone alone. The one report of abortion reversal was a case series of 7 patients receiving varying doses of progesterone in oil intramuscularly or micronized progesterone orally or vaginally; 1 patient was lost to follow-up. The study was of poor quality and lacked clear information on patient selection. Four of six women continued the pregnancy to term [67%, 95% confidence interval (CI) 30– 90%]. Assuming the lost patient aborted resulted in a continuing pregnancy proportion of 57% (95% CI 25–84%). The proportion of pregnancies continuing 1–2 weeks after mifepristone alone varied from 8% (95% CI 3–22%) to 46% (95% CI 37–56%). Continuing pregnancy was more common with lower mifepristone doses and advanced gestational age. Conclusions: In the rare case that a woman changes her mind after starting medical abortion, evidence is insufficient to determine whether treatment with progesterone after mifepristone results in a higher proportion of continuing pregnancies compared to expectant management. Implications: Legislation requiring physicians to inform patients about abortion reversal transforms an unproven therapy into law and represents legislative interference in the patient–physician relationship. © 2015 Elsevier Inc. All rights reserved.

Ultraviolet radiation (UVR) has been an effective treatment for a number of chronic skin disorders, and its ability to alleviate these conditions has been well documented. Although nonionizing, exposure to ultraviolet (UV) radiation is still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions treated with this therapy tend to be chronic, exposures are repeated and can be high, increasing the lifetime probability of an adverse event or mutagenic effect. Despite the potential detrimental effects, quantitative ultraviolet dosimetry for phototherapy is an underdeveloped area and better dosimetry would allow clinicians to maximize biological effect whilst minimizing the repercussions of overexposure. This review gives a history and insight into the current state of UVR phototherapy, including an overview of biological effects of UVR, a discussion of UVR production, illness treated by this modality, cabin design and the clinical implementation of phototherapy, as well as clinical dose estimation techniques. Several dose models for ultraviolet phototherapy are also examined, and the need for an accurate computational dose estimation method in ultraviolet phototherapy is discussed.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed.

Beginning in the 1960s depot medroxyprogesterone acetate (DMPA) injectable contraception has been widely used in family planning programs abroad especially in Africa and Southeast Asia [1]. Approved in the US for the treatment of endometrial cancer in the mid-1960s it was also used off-label for contraception [2]. In 1992 DMPA received Food and Drug Administration (FDA) approval for contraception and began to have a noticeable impact in preventing unintended pregnancies in the US particularly among teens. By 2002 some 2 million US women used injectable contraception [3]. Whereas US teen births increased 23% from 1986 peaking in 1991 rates then declined 35% by 2005 [4]. The authors of the 2002 National Survey of Family Growth (NSFG) reported that “Teens were more likely in 2002 to use contraception at first sex and at most recent sex than in 1995 and were more likely to have used highly effective methods such as injectable contraception” [5]. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Opinion www. AJOG .org GENERAL GYNECOLOGY A statement on abortion by 100 professors of obstetrics: 40 years later One Hundred Professors of Obstetrics and Gynecology F orty years ago, leaders in obstetrics and gynecology published a com- pelling statement that recognized the legalization of abortion in several states and anticipated the 1973 Supreme Court decision in Roe v Wade (Supplementary Data available at www.AJOG.org). 1 They projected the numbers of legal abortions that likely would be required by women in the United States and described the role of the teaching hospital in meeting that responsibility. 1 They wrote to ex- press their concern for women’s health in a new legal and medical era of re- productive control and to define the responsibilities of academic obstetrician- gynecologists. Since then, we have advanced the fields of reproduction and family planning. Thanks to these developments, women can now prevent pregnancy with safer and more effective forms of contracep- tion (most recently long-acting revers- ible methods), with simple and sensitive hormonal and sonographic methods to determine pregnancy status and dura- tion, and with new methods of infer- tility treatment and prenatal testing that rely on the option of terminating inten- ded pregnancies that are diagnosed as abnormal. To terminate pregnancies, cli- nicians now use misoprostol and mife- pristone for “medical abortion” (which in 2009 accounted for 16.5% of termina- tions in the United States and can be office-based) and use sonographic guid- ance of intrauterine procedures along with new methods for inducing cervical From the 100 Professors (Appendix). Received Dec. 3, 2012; revised Jan. 23, 2013; accepted March 7, 2013. The author reports no conflict of interest. Reprints not available from the authors. a 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.03.007 In this Journal in 1972, 100 leaders in obstetrics and gynecology published a compelling statement that recognized the legalization of abortion in several states and anticipated the 1973 Supreme Court decision in Roe v Wade. They projected the numbers of legal abortions that likely would be required by women in the United States and described the role of the teaching hospital in meeting that responsibility. They wrote to express their concern for women’s health in a new legal and medical era of reproductive control and to define the responsibilities of academic obstetrician-gynecologists. Forty years later, 100 professors examine the statement of their predecessors in light of medical advances and legal changes and suggest a further course of action for obstetrician gynecologists. Key words: abortion, law, teaching hospital dilation and uterine contraction; patients benefit from innovations in counseling and new approaches to pain control. 2-6 Studies of abortion practice and out- comes are also much more sophisticated than they were 40 years ago. 7,8 We have had 40 years of medical progress but have witnessed political regression that the 100 professors did not anticipate. In 2011 alone, 24 states passed 92 legislative restrictions on abortion. 9 Waiting periods after consent are now law in 26 states. Alabama, Arizona, Florida, Kansas, Louisiana, North Car- olina, Oklahoma, and Texas require pa- tients to view ultrasound images and, in Arizona, Louisiana, Mississippi, and Texas, to listen to fetal heart beats. 10 Laws in 27 states force physicians to provide deceptive counseling including false statements about risks of breast cancer, infertility, and mental health. They include laws to limit second-trimester abortion under the guise of protecting the fetus from pain (Alabama, Idaho, Indiana, Kansas, Louisiana, Nebraska, and Oklahoma). 11 Laws directed specif- ically at medical education in Arizona, Kansas, and Texas prohibit abortion training in public institutions and another 7 states ban abortion in public hospitals, precluding training in them. 12 What vision of the future of legalized abortion did the 100 professors have? How accurately did they estimate the need for safe, legal abortion and antici- pate their colleagues’ willingness and commitment to meeting it? They wrote, “In view of the impending change in abortion practices generated by new state legislation and federal court de- cisions, we believe it helpful to [respond] to this increasingly liberal course of events.by contributing to the solution of an imminent problem.” 1 Forty years later, the change is not liberal. Its effects will threaten, not improve, women’s health and already obstruct physicians’ evidence-based and patient-centered practices. We review our predecessors’ 1972 statement and judge how it com- ports with what actually occurred and with legislation that has been adopted over the 40 years since their writing and the passage of Roe v Wade. The 100 professors were remarkably prescient in anticipating the need for 1 million legal abortions and today’s abortion rate of 1 in 4 pregnancies. 13,14 They predicted that teaching hospitals with specialized outpatient facilities could meet the demand and believed that abortions were the responsibility of hospitals. But today, 90% of abortions, which include the 10% that are in the second trimester, are done away from hospitals. 15 Many hospitals enforce fetal and maternal health restrictions that SEPTEMBER 2013 American Journal of Obstetrics & Gynecology

Correctly diagnosing pelvic inflammatory disease (PID) using noninvasive clinical criteria remains challenging. Current guidelines for initiating treatment, based on minimal criteria (sensitive but not specific), are justified for public health purposes but inadequate and misleading for scientific purposes. Previous research on the link between the intrauterine device (IUD) and PID was controversial and subject to many limitations. Even today, these limitations still exist and include uncertainty of the PID diagnosis, unfair contraceptive comparisons, selection and diagnostic bias, and confounding. For example, IUD users are on heightened alert for PID relative to users of other methods. In addition, IUD users with pelvic pain may be more likely to seek physician consultation and consequently receive a PID diagnosis (true-positive or false-positive). Confounding factors such as higher coital frequency, multiple sexual partners, and low condom use may explain any finding that shows a higher PID rate among IUD users compared with other contraceptive users. Good evidence on how or whether the IUD changes the etiology of PID is lacking. In the past 10 years, use of the intrauterine device in the United States has increased markedly. Thus today, researchers may now have sufficient population-level exposure (IUD use) and disease (PID) to search for a connection and repeat past mistakes. Any new findings using observational research should be interpreted with caution. More rigorous research designs may not be pragmatic or feasible.

OBJECTIVE: : Screening for inherited thrombophilias with laboratory tests is impractical before starting women on combined oral contraceptives. As an alternative some recommend eliciting a family history of venous thromboembolism. The validity of this approach however remains unclear. DATA SOURCES: : We sought all published reports that correlated a family history of venous thromboembolism with any thrombophilia confirmed by laboratory test. We used sequential overlapping computer searches including MeSH terms used for articles in PubMed a narrative search phrase in Google Scholar and then all "related" articles in PubMed for each article included without time or language limitations. This was supplemented by a search of www.clinicaltrials.gov. METHODS OF STUDY SELECTION: : The search yielded 10 reports. Information was sought without success from corresponding authors of four other reports that may have had relevant data. Most reports studied atypical high-prevalence referral populations. TABULATION INTEGRATION AND RESULTS: : Results were presented according to the MOOSE (Meta-analysis of observational studies in epidemiology) guidelines for systematic reviews of observational studies. The patient populations varied widely definitions of family history included first- or first- and second-degree relatives and the thrombophilias studied differed among these reports. Hence aggregation of results was not possible. Despite these differences all reports consistently documented poor validity of family history for detecting thrombophilias. Sensitivity ranged from 16% to 63% and positive predictive value from 6% to 50% for the various thrombophilias studied. In no study did family history meet the benchmark for a good test (sensitivity plus specificity greater than 150%). CONCLUSION: : Obtaining a family history of venous thromboembolism before starting combined oral contraceptives is not a valid means to detect a womans risk of thrombophilia. Even in high-prevalence populations in which the positive predictive value is increased a positive family history of venous thromboembolism was no better than flipping a coin in predicting thrombophilia.

Background Homeopathy is a system of complementary and alternative medicine based on a belief that a malady can be treated by the administration of an extreme dilution of an agent thought to cause the physical signs of that malady. Homeopathy enjoys popular support from the general public and advocates of alternative medicine, but most large-scale clinical trials show no homeopathy to be no more effective than placebo treatment. Objectives To explore the chemical and physical plausibility of homeopathic treatments. Methods Homeopathic claims were put into a physical context and analysed using the laws of basic physics and chemistry. Results Through the laws of physics, homeopathic medicines appear to have zero chance of containing any biologically active component. Evidence from physical chemistry also rules out the plausibility of mechanisms such as water memory. Conclusions The proposed mechanisms of homeopathy are shown to be implausible when analysed from a physical and chemical perspective, and thus it is of no surprise that the biological effects of homeopathy cannot be measured in large-scale clinical trials.

Feticidal injection of digoxin before dilation and Level II studies have a control group and thus allow evacuation (D&E) abortion has become common in recent years and is now a standard policy at some abortion clinics. The procedure entails amniocentesis and administration of digoxin into the amniotic fluid or fetus before uterine evacuation. Two new reports in this issue of the journal present conflicting views about its safety [1,2]. An invasive procedure, amniocentesis causes pain and incurs cost, inconvenience and risk. Hence, clear justification is needed for it to be used routinely. Several rationales, discussed below, have been invoked for digoxin injection before D&E.

In early pregnancy, medical abortion avoids surgery but is associated with more pain and bleeding and a slightly higher risk of incomplete abortion. Data show that neither type of abortion increases the risk of long-term mental health problems or breast cancer or adversely affects fertility.

Background Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women. Objectives To determine the effectiveness of combined oral contraceptives (COCs) for the treatment of facial acne compared to placebo or other active therapies. Search strategy We searched for randomized controlled trials of COCs and acne in the computerized databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, and LILACS. We also searched for clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We wrote to authors of identified trials to seek any unpublished or published trials that we might have missed. Selection criteria All randomized controlled trials reported in any language that compared the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women were eligible. Data collection and analysis We extracted data on total and specific (i.e., open or closed comedones, papules, pustules and nodules) facial lesion counts; acne severity grades; global assessments by the clinician or the participant and discontinuation due to adverse events. Data were entered and analyzed in RevMan. Main results The search yielded 25 trials: 7 placebo-controlled trials made 4 different comparisons, 17 trials made 13 comparisons between 2 different COC regimens, and 1 additional trial compared a COC to an antibiotic. COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo. Differences in the comparative effectiveness of COCs containing varying progestin types and dosages, though, were less clear. COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel, although this apparent advantage was based on limited data. A COC with cyproterone acetate might result in better acne outcomes than one with desogestrel; however, the three studies comparing these COCs produced conflicting results. Likewise, levonorgestrel showed a slight improvement over desogestrel in acne outcomes in one trial, but a second trial found the COC groups were similar. Authors' conclusions The four COCs evaluated in placebo-controlled trials are effective in reducing inflammatory and non-inflammatory facial acne lesions. Few important differences were found between COC types in their effectiveness for treating acne. How COCs compare to alternative acne treatments is unknown since limited data were available regarding this question. Plain Language Summary Effect of birth control pills on acne in women Acne is a common skin problem for women. Several treatments are available. Combined birth control pills, which have the hormones estrogen and progestin, are often prescribed for women with acne. This review looked at how well birth control pills worked to treat facial acne. We did a computer search for studies of birth control pills and acne treatment. Outcomes could be the amount of acne, how severe the acne was, and how many women dropped out early due to problems. We wrote to researchers to find other trials. We included randomized trials in any language that compared two types of birth control pills, a pill and a placebo or 'dummy,' or a pill and another acne treatment. We found 25 trials: 7 trials used 'dummies,' 17 compared different types of birth control pills, and 1 compared a pill and an antibiotic. The three pills studied in trials with dummies worked well to reduce facial acne. In comparing pills with different hormones, no important differences were seen. The conclusions did not change when we added trials in this update to the other studies. Most trials compared two types of pills for acne treatment. Better quality studies are needed to compare one birth control pill with another. How birth control pills compare to other acne treatments like antibiotics is unclear. Since birth control pills improve acne, they can be used to treat women with acne who also want birth control.

To compare the safety and effectiveness of dilation and evacuation (DE) and labor-induction abortion performed for fetal anomalies or fetal death in the second trimester.We performed a retrospective cohort study of second-trimester abortions performed for fetal indications. We compared the frequency of complications and effectiveness of abortions performed at 13-24 weeks for these indications. We calculated proportions of patients with complications for these two methods and controlled for confounding using a log binomial model.Labor-induction abortions had higher complication rates and lower effectiveness than did DE. Thirty-two of 136 women undergoing labor induction (24%) experienced one or more complications, in contrast to 9 of 263 women (3%) undergoing DE (unadjusted relative risk 6.9 [95% confidence interval 3.4-14.0]). When controlled for confounding, the adjusted risk ratio for labor induction was 8.5 (95% confidence interval 3.7-19.8) compared with DE.Dilation and evacuation is significantly safer and more effective than labor induction for second-trimester abortion for fetal indications. Bias and chance are unlikely explanations for these large discrepancies. Women facing this difficult decision should be offered a choice of methods and be provided information about their comparative safety and effectiveness.II.

Purpose: Ultraviolet phototherapy is widely used in the treatment of numerous skin conditions. This treatment is well established and largely beneficial to patients on both physical and psychological levels; however, overexposure to ultraviolet radiation (UVR) can have detrimental effects, such as erythemal responses and ocular damage in addition to the potentially carcinogenic nature of UVR. For these reasons, it is essential to control and quantify the radiationdose incident upon the patient to ensure that it is both biologically effective and has the minimal possible impact on the surrounding unaffected tissue. Methods: To date, there has been little work on dose modeling, and the output of artificial UVR sources is an area where research has been recommended. This work characterizes these sources by formalizing an approach from first principles and experimentally examining this model. Results: An implementation of a line source model is found to give impressive accuracy and quantifies the output radiation well. Conclusions: This method could potentially serve as a basis for a full computational dose model for quantifying patient dose.

Sino-implant (II) is a subdermal contraceptive implant manufactured in China. This two-rod levonorgestrel-releasing implant has the same amount of active ingredient (150 mg levonorgestrel) and mechanism of action as the widely available contraceptive implant Jadelle. We examined randomized controlled trials of Sino-implant (II) for effectiveness and side effects.We searched electronic databases for studies of Sino-implant (II) and then restricted our review to randomized controlled trials. The primary outcome of this review was pregnancy.Four randomized trials with a total of 15,943 women assigned to Sino-implant (II) had first-year probabilities of pregnancy ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the 4 years of the product's approved duration of use were 0.9% and 1.06% in the two trials that presented date for 4-year use. Five-year cumulative probabilities of pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may be why the implant is approved for 4 years of use in China. Five-year cumulative probabilities of discontinuation due to menstrual problems ranged from 12.5% to 15.5% for Sino-implant (II).Sino-implant (II) is one of the most effective contraceptives available today. These available clinical data, combined with independent laboratory testing, and the knowledge that 7 million women have used this method since 1994, support the safety and effectiveness of Sino-implant (II). The lower cost of Sino-implant (II) compared with other subdermal implants could improve access to implants in resource-constrained settings.

Decades after its introduction, dilatation and evacuation (D&E) is still not universally offered by gynaecologists who provide second trimester abortion. Three lines of evidence point to D&E as the preferred method for most women. First, the uterus has evolved to expel its contents early and late in pregnancy, not in the middle. Hence, induction of labour with medical abortion forces the uterus to perform a task it is not designed to do. Second, cohort studies and randomised, controlled trials over the past 30 years have consistently shown that D&E is safer and more effective than labour induction abortion, regardless of the abortifacient used. Third, the ethical principles of beneficence, autonomy and justice require that D&E be routinely offered by gynaecologists who perform second trimester abortions. The uneven geographical availability of D&E may stem from lack of information, lack of requisite equipment and training, or lack of motivation. According to the principles of evidence-based medicine and bioethics, these barriers to better care for women can and should be overcome.

In countries where levonorgestrel-releasing IUD use has increased the incidence of female surgical sterilization procedures has decreased. Will the same inverse relationship appear in the United States and if so what would be the medical implications of such a transition in long-term contraception? A recent UK review compared long-term contraception with IUDs vs. surgical sterilization; here we compare these two approaches from a US perspective. We focus on interval tubal sterilization by laparoscopy or laparotomy and will not consider postpartum sterilization. (excerpt)

Die reiche Geschichte der Verblindung erstreckt sich uber zwei Jahrhunderte. Weltweit wissen die meisten Wissenschaftler, was mit Verblindung gemeint ist, doch hinter einem nur allgemeinen Verstandnis lauert oftmals Verwirrung. Begriffe wie einfachblind, doppelblind und dreifachblind haben fur verschiedene Personen unterschiedliche Bedeutung. Auserdem verwechseln viele medizinische Forscher die Verblindung mit der Geheimhaltung der Randomisierungsliste. Solche Verwechslungen zeigen, dass beide Begriffe missverstanden werden. Verblindung bedeutet, das Studienteilnehmer, Studienarzte (meist diejenigen, die die Behandlung verabreichen) oder Bewerter (diejenigen, die die Outcome-Daten erheben) die zugeteilte Intervention nicht kennen, sodass sie durch dieses Wissen nicht beeinflusst werden. Im Allgemeinen fuhrt die Verblindung zu einem Ruckgang der unterschiedlichen Bewertung von Behandlungsergebnissen (Informationsbias). Sie kann bei den Studienteilnehmern aber auch die Compliance und die Bereitschaft zum Verbleib in der Studie verbessern, wahrend sie die Anwendung zusatzlicher Pflege- oder Therapiemasnahmen (manchmal als Ko-Intervention bezeichnet) reduziert. Studienarzte und Leser gehen vielfach gutglaubig davon aus, dass eine randomisierte Studie einfach dann als hochwertig anzusehen ist, wenn sie doppelt verblindet wurde, als ob es sich bei der doppelten Verblindung um die Conditio sine qua non einer randomisierten, kontrollierten Studie handelte. Auch wenn die Doppelverblindung (Verblindung von Studienarzten, Studienteilnehmern und Bewertern der Behandlungsergebnisse) auf eine solide Studienplanung schliesen lasst, durfen Studien ohne Doppelverblindung nicht automatisch als minderwertig eingestuft werden. Anstatt sich ausschlieslich auf Begriffe wie Doppelverblindung zu verlassen, sollten Wissenschaftler explizit angeben, wer wie verblindet wurde. Wir empfehlen, den Ergebnissen mehr Glauben zu schenken, wenn zumindest die Bewertung der Studienergebnisse verblindet erfolgte, mit Ausnahme von objektiven Endpunkten wie etwa der Mortalitat, die kaum Raum fur systematische Fehler (Bias) lassen. Wenn Studienarzte ihre Verblindungsmasnahmen korrekt angeben, kann der Leser sie beurteilen. Leider lasst die Berichterstattung in vielen Artikeln zu wunschen ubrig. Wenn in einem Beitrag behauptet wird, es habe eine Verblindung stattgefunden, ohne dies weiter zu erklaren, sollte der Leser hinsichtlich ihrer Bias reduzierenden Wirkung skeptisch bleiben.

Summary Ending the silent pandemic of unsafe abortion is an urgent public-health and human-rights imperative. As with other more visible global-health issues, this scourge threatens women throughout the developing world. Every year, about 19–20 million abortions are done by individuals without the requisite skills, or in environments below minimum medical standards, or both. Nearly all unsafe abortions (97%) are in developing countries. An estimated 68 000 women die as a result, and millions more have complications, many permanent. Important causes of death include haemorrhage, infection, and poisoning. Legalisation of abortion on request is a necessary but insufficient step toward improving women's health; in some countries, such as India, where abortion has been legal for decades, access to competent care remains restricted because of other barriers. Access to safe abortion improves women's health, and vice versa, as documented in Romania during the regime of President Nicolae Ceausescu. The availability of modern contraception can reduce but never eliminate the need for abortion. Direct costs of treating abortion complications burden impoverished health care systems, and indirect costs also drain struggling economies. The development of manual vacuum aspiration to empty the uterus, and the use of misoprostol, an oxytocic agent, have improved the care of women. Access to safe, legal abortion is a fundamental right of women, irrespective of where they live. The underlying causes of morbidity and mortality from unsafe abortion today are not blood loss and infection but, rather, apathy and disdain toward women.

The Fertility Regulation Group of the Cochrane Collaboration has been assessing the best available evidence on fertility regulation, family size and birth spacing. By the end of 2005, this group had published 32 systematic reviews and 12 protocols; most reviews were on contraception. Because of suboptimal trial quality, firm conclusions could be made in only five reviews. Threats to internal validity in published trials include the absence of description of allocation concealment, intentional exclusion of participants after randomization, failure to use intention-to-treat analyses and lack of treatment blinding. The precision of results has been limited by small sample sizes. The finding that most trials of oral contraceptives were conducted by pharmaceutical companies raises concerns about potential commercial bias. Of necessity, most information about fertility regulation effectiveness and adverse effects comes from observational studies, which vary widely in quality. Systematic reviews of evidence, with an emphasis on randomized controlled trials when available, will continue to improve fertility regulation in the years ahead.

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.

Likelihood ratios can refine clinical diagnosis on the basis of signs and symptoms; however, they are underused for patients' care. A likelihood ratio is the percentage of ill people with a given test result divided by the percentage of well individuals with the same result. Ideally, abnormal test results should be much more typical in ill individuals than in those who are well (high likelihood ratio) and normal test results should be most frequent in well people than in sick people (low likelihood ratio). Likelihood ratios near unity have little effect on decision-making; by contrast, high or low ratios can greatly shift the clinician's estimate of the probability of disease. Likelihood ratios can be calculated not only for dichotomous (positive or negative) tests but also for tests with multiple levels of results, such as creatine kinase or ventilation-perfusion scans. When combined with an accurate clinical diagnosis, likelihood ratios from ancillary tests improve diagnostic accuracy in a synergistic manner.

Objective Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women. Methods We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well. Results Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months. Conclusion The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized. Level of evidence I.

Summary Investigators should properly calculate sample sizes before the start of their randomised trials and adequately describe the details in their published report. In these a-priori calculations, determining the effect size to detect—eg, event rates in treatment and control groups—reflects inherently subjective clinical judgments. Furthermore, these judgments greatly affect sample size calculations. We question the branding of trials as unethical on the basis of an imprecise sample size calculation process. So-called underpowered trials might be acceptable if investigators use methodological rigor to eliminate bias, properly report to avoid misinterpretation, and always publish results to avert publication bias. Some shift of emphasis from a fixation on sample size to a focus on methodological quality would yield more trials with less bias. Unbiased trials with imprecise results trump no results at all. Clinicians and patients deserve guidance now.

Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). This review of randomized controlled trials tested the hypothesis that COCs containingor=20 microg ethinyl estradiol (EE) perform similarly to those containing20 microg in terms of contraceptive effectiveness, bleeding patterns, discontinuation and side effects. Data from the 18 eligible trials conducted to date are inadequate for detecting possible differences in contraceptive effectiveness. Several COCs containing 20 microg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea/infrequent bleeding and irregular, prolonged, frequent bleeding or breakthrough bleeding or spotting) than their higher-estrogen comparison pills. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. While health care providers and women might select COCs containing 20 microg EE based on theoretical improvements in safety profile from the reduced dose of estrogen, no evidence is available to support this choice.

Routine follow-up visits after abortion are intended to confirm that the abortion is complete and to diagnose and treat complications. Many clinicians also take advantage of the follow-up visit to provide general reproductive health care: discussing contraceptive plans and providing family planning services; diagnosing sexually transmitted infections; performing a Pap test or discussing abnormal Pap results. We reviewed the evidence related to the routine postabortion follow-up visit. Other than mifepristone medical abortion performed at 50 days of gestation or later and methotrexate medical abortion, we found little evidence that mandatory follow-up visits typically detect conditions that women themselves could not be taught to recognize. In addition, the natural history of the most severe complications after abortion-infection and unrecognized ectopic pregnancy-have time courses inconsistent with the usual timing of the follow-up visit. Costs associated with this visit can be great. These include travel expenses, lost wages, child-care expenses, privacy and emotional burdens for women, and scheduling disruptions and the related opportunity costs caused by "no-shows" for the provider. Follow-up appointments should be scheduled for those women likely to benefit from a physical examination. For the remainder of women, simple instructions and advice about detecting complications, possibly coupled with telephone follow-up, might suffice. Although arguably valuable in their own right, counseling, family planning services, or sexually transmitted infection diagnosis and treatment should not be so inflexibly bundled with postabortion care. Protocols that require in-person follow-up after abortion may not make the best use of a women's time or abilities, or of the medical system.

Objective Many women and clinicians believe that combination estrogen-progestin contraceptive use can lead to weight gain. This concern can deter women from starting hormonal contraception or lead to premature quitting. This review evaluated the association between combination contraceptive use and change in body weight. Data sources The computerized databases CENTRAL, MEDLINE, EMBASE, Popline, and LILACS (from their inception to 2002) were used to conduct this review. Known investigators and manufacturers were contacted for information about other trials not discovered in the database search. Methods of study selection All English-language, randomized controlled trials measuring weight change that were at least 3 treatment cycles in duration and that compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length were eligible for inclusion. Of the 570 reports of randomized controlled trials of eligible interventions that were identified, 42 trials were included in the systematic review. Tabulation, integration, and results Two reviewers independently abstracted data from the eligible trials using a standard form. Depending on the data available, the weighted mean difference using a fixed effect model with 95% confidence intervals was calculated for the mean change in weight between baseline and posttreatment measurements or the Peto odds ratio with 95% confidence intervals was calculated by using the proportion of women who gained or lost more than a specified amount of weight. The 3 placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons from the 40 trials that compared 2 or more combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups when this factor was studied. Conclusion Available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.

Objective To evaluate whether patient histories of gynecological infections predict tubal pathology seen at laparoscopic exam in infertile women. Design Cross-sectional analysis from a subset of case-control subjects. Setting Tertiary-level public hospitals with infertility clinics, Mexico City. Patient(s) Three hundred twenty-one nulligravid infertile women seeking diagnostic workup. Intervention(s) Interviews conducted before evaluation by laparoscopy. Main outcome measure(s) Sensitivity, specificity, and predictive values for correlating previous pelvic inflammatory disease symptoms, vaginal discharge, genital tract infections, and antibodies to Chlamydia trachomatis to confirmed diagnoses of tubal pathology and to severe tubal pathology. Result(s) Tubal pathology was found in 58% of participants (n = 185), and severe pathology was found in 29% (n = 92). None of the historical infection-related factors alone was a good overall predictor of tubal pathology; high sensitivity values (up to 73%) were offset by low specificity (down to 30%) and vice versa, for each factor. When considered simultaneously, the factors improved the overall predictive ability just slightly (84% sensitivity and 29% specificity) over the individual factors. The validity measures did not improve when examining severe tubal pathology alone. Conclusion(s) History taking related to past genital tract infections appears to be of little use in the evaluation of infertile women.

Objective To test the feasibility of mounting a randomised controlled trial comparing mifepristone–misoprostol versus dilation and evacuation (D&E) for midtrimester abortion. Design Pilot randomised controlled trial. Setting University of North Carolina Hospitals, Chapel Hill, North Carolina. Population Women aged 18 years or older and without prior uterine operations who requested abortion at 14–19 menstrual weeks of gestation from January 2002 to January 2003. Methods Participants received either mifepristone 200 mg by mouth followed in two days by vaginal then oral misoprostol (Aberdeen regimen) or D&E after one or two days of laminaria preparation. Care was provided by residents under faculty supervision. Main outcome measures Enrolment rate and acceptability of and adverse events associated with methods. Results The trial was stopped at one year because of slow enrolment. Of 47 women eligible for the trial, 29 (62%) declined participation, primarily because of a preference for D&E abortion. Among the 18 participants enrolled, nine were randomised to treatment with mifepristone–misoprostol and 9 to D&E. Compared with D&E, mifepristone–misoprostol abortion caused more pain and adverse events, although none was serious. Conclusions Our findings concerning acceptability and adverse events should be considered hypothesis-generating; they may prove useful in planning a larger randomised controlled trial. Such a trial will be difficult to mount in the US. Hence, we suggest that it be done in a setting where labour-induction abortion is the norm.

Contraception choices may be limited for lactating women due to concerns about hormonal effects on quality and quantity of milk, passage of hormones to the infant and infant growth. We conducted a systematic review of randomized controlled trials to determine the effect of hormonal contraception on lactation. We sought all randomized controlled trials, reported in any language, that included any form of hormonal contraception compared with another form of hormonal contraception, nonhormonal contraception or placebo during lactation. Seven reports from five randomized controlled trials met the inclusion criteria. Most of the five trials did not specify their method used to generate a random sequence, method of allocation concealment, blinding of treatments or use of an intention-to-treat analysis. Additionally, high loss-to-follow-up rates invalidated at least two trials. The findings from two trials comparing oral contraceptives to placebo during lactation were conflicting. Another trial found no inhibitory effects on lactation from progestin-only contraceptives. Finally, the World Health Organization trial found a statistically significant decline in breast milk volume in women using combined oral contraceptives compared to women using progestin-only pills. However, infant growth for the two groups did not differ. The limited evidence from randomized controlled trials on the effect of hormonal contraceptives during lactation is of poor quality and insufficient to establish an effect of hormonal contraception, if any, on milk quality and quantity. At least one properly conducted randomized controlled trial of adequate size is urgently needed to make recommendations regarding hormonal contraceptive use for lactating women.

UNLABELLED The impact of lactation on maternal weight after delivery remains unclear. To address this question, we performed a systematic review of the literature. We searched PubMed, POPLINE, EMBASE, and LILACS computerized databases for relevant articles and classified the evidence using the U.S. Preventive Services Task Force rating system. We found 42 studies, of which 28 contained relevant information: 15 prospective cohort studies, 1 retrospective cohort study, 1 cross-sectional study, and 11 case-series reports. The methods used in these studies varied widely, thus precluding aggregation of results. Level II-2 and III evidence supports a class "C" recommendation: insufficient evidence exists to support an effect of lactation on maternal weight after delivery. Better longitudinal studies with a clear definition of breast-feeding; clear, specific outcome measures; study periods extending 1 or 2 years after delivery; and better control of potentially confounding factors will be needed to resolve this question. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES After completion of this article, the reader will be able to compile the literature on the effect of lactation on maternal weight, to compare the various studies, and to summarize the data on the effect of lactation on maternal weight gain.

The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm. Unlike the diaphragm, the sponge can be used for more than one coital act within 24 h without the insertion of additional spermicide, and it does not require fitting or a prescription from a physician. We conducted a systematic review of randomized controlled trials that compared the vaginal contraceptive sponge with the diaphragm used with a spermicide in order to evaluate the efficacy and continuation rates of the two devices. The sponge was statistically significantly less effective in preventing overall pregnancy than was the diaphragm in the two trials that met our inclusion criteria. The 12-month cumulative life table termination rates per 100 women for overall pregnancy were 17.4 for the sponge versus 12.8 for the diaphragm in the larger US trial, and 24.5 for the sponge and 10.9 for the diaphragm in the UK trial. Similarly, discontinuation rates at 12 months were higher with the sponge than with the diaphragm [odds ratio 1.3; 95% confidence interval (CI) 1.1-1.6]. Allergic-type reactions were more common with the sponge in both trials, although the frequency of discontinuation for discomfort differed in the two trials. Other randomized controlled trials will be needed to resolve the role of spermicides in preventing sexually transmitted infections or in causing adverse effects.

The premature termination of one comparison in the Women's Health Initiative primary prevention trial due to stopping rules being reached necessitates a reconsideration of hormone replacement therapy (HRT). This part of the Women's Health Initiative trial, however, examined only one popular HRT regimen (conjugated equine estrogen [0.625 mg] and medroxyprogesterone acetate [2.5 mg] daily) in asymptomatic postmenopausal women. To help clinicians understand this large, complex trial, we describe several pervasive biases in earlier observational studies, review the principal findings of the trial, summarize recent systematic reviews, and offer clinical suggestions for HRT. Observational studies of HRT have found consistent, powerful protection against heart disease; this now appears due to consistent, powerful selection biases. These biases have the same net effect: Women using HRT in observational studies were healthier than those not using it. The Women's Health Initiative trial found that the overall risk-benefit ratio tipped against using HRT for prevention. Cardiovascular disease and breast cancer were increased among users, whereas colorectal cancer and osteoporotic fractures were reduced. Whether these findings relate to women with menopausal symptoms and to different HRT regimens is unknown. Hormone replacement therapy remains the best treatment for menopausal symptoms. Although estrogen has proven benefit for osteoporosis prevention, alternatives include raloxifene, alendronate, and risedronate. For women needing HRT, use of a low dose, with reassessments at least annually, appears prudent. Heart disease prevention strategies of proven value include exercise, weight control, blood pressure and lipid control, and avoidance of smoking. Hormone replacement therapy should not be used for this purpose.

Hormonal emergency contraception is safe, effective, and available by prescription in the United States. This article explains why dropping the prescription requirement for emergency contraception would pose no risk to women and would improve public health by preventing unintended pregnancies. The author points out that over-the-counter sale of emergency contraceptive products is appropriate, because women are easily able to determine when and how to use them.

In the early 1800s, Karl Baedeker, a German publisher, launched a series of travel guidebooks. By the twentieth century, the guidebooks had achieved such international fame that his name became synonymous with the genre. As clinicians wade into the flood of clinical research being published, a guidebook can be a handy navigational aid. In this article, we offer a Baedeker for reading the literature, an approach distilled from our three decades of clinical practice and research experience. Interested readers can find more detail in our recent series on research methods in The Lancet (1–11). Reading research is mandatory if a clinician is to keep up. With greater age and experience, clinical practice should improve. Paradoxically, however, greater age and clinical experience often translate into rusty practice. As has been shown for treatment of hypertension, one of the strongest determinants of appropriate practice is number of years since medical school graduation; stated alternatively, practice quality deteriorates over time (12, 13). Keeping current is difficult after leaving formal training, and that difficulty may be greater for those who practice in smaller communities (14). If one cannot (or chooses not to) read, then one’s practice is condemned to becoming obsolete. This indirectly hurts patients. A second benefit of critical reading of clinical research is appropriate adoption (or rejection) of new technologies. Obstetrics and gynecology has a long, blemished record of adoption and dissemination of new tests and procedures without evidence of benefit (15). Episiotomy, one of the most common operations performed on adults in the last century, swept into practice based on DeLee’s analogy that childbirth is tantamount to impalement on a pitchfork (16). Urinary estriol measurement to monitor a fetus thought to be in jeopardy has been replaced by an even more expensive and cumbersome test (nonstress testing) for which no evidence of benefit exists either (17). Electronic fetal monitoring took U.S. obstetrics by storm in the absence of demonstrable benefit; a quarter century of study has failed to show any lasting benefit to babies (18), and the poor predictive value of worrisome tracings has needlessly driven up the cesarean delivery rate. Liquid-based cervical cytology screening has not been shown to reduce cervical cancer incidence or mortality, and the cost per case of cancer detected is higher with this approach than with conventional cytology (19). Ironically, poor women at highest risk of this cancer may not be able to afford the screening (20). Reports of new laparoscopy operations have recently been retracted by an editor, because the reported information could not be corroborated (21, 22). This hurt patients as well. While reading clinical research is clearly important, the task is daunting. First, the volume being published is overwhelming, with an estimated 25,000 biomedical journals in print. One challenge is picking and choosing what to read. In general, most readers should limit themselves to articles that are both relevant to their practices and likely to be of high scientific value. These two criteria will immediately narrow the field. Once an article is selected, another problem emerges: many clinicians in obstetrics and gynecology report that they cannot critically read the literature (23). Our graduates leave their training full of the Correspondence to: Family Health International, P.O. Box 13950, Research Triangle Park, NC 27709. Email: dgrimes@fhi.org

Summary Proper randomisation means little if investigators cannot include all randomised participants in the primary analysis. Participants might ignore follow-up, leave town, or take aspartame when instructed to take aspirin. Exclusions before randomisation do not bias the treatment comparison, but they can hurt generalisability. Eligibility criteria for a trial should be clear, specific, and applied before randomisation. Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested. In principle, assessment of exclusions after randomisation is simple: none are allowed. For the primary analysis, all participants enrolled should be included and analysed as part of the original group assigned (an intent-to-treat analysis). In reality, however, losses frequently occur. Investigators should, therefore, commit adequate resources to develop and implement procedures to maximise retention of participants. Moreover, researchers should provide clear, explicit information on the progress of all randomised participants through the trial by use of, for instance, a trial profile. Investigators can also do secondary analyses on, for instance, per-protocol or as-treated participants. Such analyses should be described as secondary and non-randomised comparisons. Mishandling of exclusions causes serious methodological difficulties. Unfortunately, some explanations for mishandling exclusions intuitively appeal to readers, disguising the seriousness of the issues. Creative mismanagement of exclusions can undermine trial validity.

Most women and their clinicians are unaware that IUDs confer important noncontraceptive health benefits. This review summarizes the evidence from published articles on this topic. We conducted a series of systematic literature searches to identify articles on the noncontraceptive health benefits of IUD use. We reviewed the potentially pertinent ones for content, grouped them according to type of IUD, and evaluated them using the U.S. Preventive Services Task Force rating system. Over 500 titles were identified and several hundred abstracts were reviewed. Use of nonhormonal IUDs (plastic and copper) was associated with a decrease in endometrial cancer. The levonorgestrel intrauterine system can treat a variety of gynecological disorders, including menorrhagia and anemia. The levonorgestrel system has also been used successfully as part of hormone replacement therapy, as adjuvant therapy with tamoxifen, and as an alternative to hysterectomy for women with bleeding problems. Like oral contraceptives, intrauterine contraceptives confer important noncontraceptive health benefits.

Summary Epidemiologists benefit greatly from having case-control study designs in their research armamentarium. Case-control studies can yield important scientific findings with relatively little time, money, and effort compared with other study designs. This seemingly quick road to research results entices many newly trained epidemiologists. Indeed, investigators implement case-control studies more frequently than any other analytical epidemiological study. Unfortunately, case-control designs also tend to be more susceptible to biases than other comparative studies. Although easier to do, they are also easier to do wrong. Five main notions guide investigators who do, or readers who assess, case-control studies. First, investigators must explicitly define the criteria for diagnosis of a case and any eligibility criteria used for selection. Second, controls should come from the same population as the cases, and their selection should be independent of the exposures of interest. Third, investigators should blind the data gatherers to the case or control status of participants or, if impossible, at least blind them to the main hypothesis of the study. Fourth, data gatherers need to be thoroughly trained to elicit exposure in a similar manner from cases and controls; they should use memory aids to facilitate and balance recall between cases and controls. Finally, investigators should address confounding in case-control studies, either in the design stage or with analytical techniques. Devotion of meticulous attention to these points enhances the validity of the results and bolsters the reader's confidence in the findings.

Background The use of an effective contraceptive may be necessary after an abortion. Insertion of an intrauterine device (IUD) may be done the same day or later. Immediate IUD insertion is an option since the woman is not pregnant, pain of insertion is less because the cervical os is open, and her motivation to use contraception may be high. However, insertion of an IUD immediately after a pregnancy ends carries risks, such as spontaneous expulsion. Objectives To assess the safety and efficacy of IUD insertion immediately after spontaneous or induced abortion. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov, and ICTRP in January 27, 2014. We also contacted investigators to identify other trials. Selection criteria We sought all randomised controlled trials (RCTs) with at least one treatment arm that involved IUD insertion immediately after an induced abortion or after curettage for spontaneous abortion. Data collection and analysis We evaluated the methodological quality of each report and abstracted the data. We focused on discontinuation rates for accidental pregnancy, perforation, expulsion, and pelvic inflammatory disease. We computed the weighted average of the rate ratios. We computed risk ratios (RRs) with 95% Confidence Intervals (CIs). We performed an intention-to-treat (ITT) analysis by including all randomised participants in the analysis according to the Cochrane Handbook for Systematic Reviews of Interventions. Main results We identified 12 trials most of which are of moderate risk of bias involving 7,119 participants which described random assignment. Five trials randomised to either immediate or delayed insertion of IUD. One of them randomised to immediate versus delayed insertion of Copper 7 showed immediate insertion of the Copper 7 was associated with a higher risk of expulsion than was delayed insertion (RR 11.98, 95% CI 1.61 to 89.35,1 study, 259 participants); the quality of evidence was moderate. Moderate quality of evidence also suggests that use and expulsion of levonorgestrel-releasing intrauterine system or CuT380A was more likely for immediate compared to delayed insertion risk ratio (RR) 1.40 (95% CI 1.24 to 1.58; 3 studies; 878 participants) and RR 2.64 ( 95% CI 1.16 to 6.00; 3 studies; 878 participants) respectively. Another trial randomised to the levonorgestrel IUD or Nova T showed discontinuation rates due to pregnancy were likely to be higher for women in the Nova T group. (MD 8.70, 95% CI 3.92 to 13.48;1 study; 438 participants); moderate quality evidence. Seven trials examined immediate insertion of IUD only. From meta-analysis of two multicentre trials, pregnancy was less likely for the TCu 220C versus the Lippes Loop (RR 0.43, 95% CI 0.24 to 0.75; 2 studies; 2257 participants ) as was expulsion (RR 0.61, 95% CI 0.46 to 0.81; 2 studies; 2257 participants). Estimates for the TCu 220 versus the Copper 7 were RR 0.42 ( 95% CI 0.23 to 0.77; 2 studies, 2,274 participants) and RR 0.68, (95% CI 0.51 to 0.91); 2 studies, 2,274 participants), respectively. In other work, adding copper sleeves to the Lippes Loop improved efficacy (RR 3.40, 95% CI 1.28 to 9.04, 1 study, 400 participants) and reduced expulsion (RR 3.00, 95% CI 1.51 to 5.97; 1 study, 400 participants). Authors' conclusions Moderate quality evidence shows that insertion of an IUD immediately after abortion is safe and practical. IUD expulsion rates appear higher immediately after abortions compared to delayed insertions. However, at six months postabortion, IUD use is higher following immediate insertion compared to delayed insertion.

Background Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. Objectives Our aim was to evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women. Search methods Through April 2014, we searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We examined reference lists of relevant articles for other trials. For the initial review, we wrote to investigators to find additional trials. Selection criteria Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover markers in women with hormonal contraceptive use prior to menopause. Eligible interventions included comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive that differed in terms of drug, dosage, or regimen. They also included providing a supplement to one group. Data collection and analysis We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to differing interventions, no trials could be combined for meta-analysis. We applied principles from GRADE to assess the evidence quality and address confidence in the effect estimates. In addition, a sensitivity analysis included trials that provided sufficient data for this review and evidence of at least moderate quality. Main results We found 19 RCTs that met our eligibility criteria. Eleven trials compared different combined oral contraceptives (COCs) or regimens of COCs; five examined an injectable versus another injectable, implant, or IUD; two studied implants, and one compared the transdermal patch versus the vaginal ring. No trial had fracture as an outcome. BMD was measured in 17 studies and 12 trials assessed biochemical markers of bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density (BMD). The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo supplement. COCs did not appear to negatively affect BMD, and some formulations had more positive effects than others. However, no COC trial was placebo-controlled. Where studies showed differences between groups in bone turnover markers, the results were generally consistent with those for BMD. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group but results were not consistent across all implant comparisons. The sensitivity analysis included 11 trials providing evidence of moderate or high quality. Four trials involving DMPA showed some positive effects of an estrogen supplement on BMD, a negative effect of DMPA-subcutaneous on lumbar spine BMD, and a negative effect of DMPA on a bone formation marker. Of the three COC trials, one had a BMD decrease for the group with gestodene plus EE 15 μg. Another indicated less bone resorption in the group with gestodene plus EE 30 μg versus EE 20 μg. Authors' conclusions Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. The evidence quality was considered moderate overall, largely due to the trials of DMPA, implants, and the patch versus ring. The COC evidence varied in quality but was low overall. Many trials had small numbers of participants and some had large losses. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Background Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. Objectives The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. Search methods In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. Selection criteria All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. Data collection and analysis All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. Main results We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied. Authors' conclusions Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non-hormonal group to control for other factors, including changes in weight over time.

Hypoxia occurs when oxygen levels within a tissue drop below normal physiological levels. In tumours, hypoxia is associated with poor prognosis, increased likelihood of metastasis and resistance to therapy. Imaging techniques, for example, positron emission tomography, are increasingly used in the monitoring of tumour hypoxia and have the potential to help in the planning of radiotherapy. For this application, improved understanding of the link between image contrast and quantitative underlying oxygen distribution would be very useful. Mathematical models of tissue hypoxia and image formation can help understand this. Hypoxia is caused by an imbalance between vascular supply and tissue demand. While much work has been dedicated to the quantitative description of tumour vascular networks, consideration of tumour oxygen consumption is largely neglected. Oxidative respiration in standard two-dimensional cell culture has been widely studied. However, two-dimensional culture fails to capture the complexities of growing three-dimensional tissue which could impact on the oxygen usage. In this study, we build on previous descriptions of oxygen consumption and diffusion in three-dimensional tumour spheroids and present a method for estimating rates of oxygen consumption from spheroids, validated using stained spheroid sections. Methods for estimating the local partial pressure of oxygen, the diffusion limit and the extents of the necrotic core, hypoxic region and proliferating rim are also derived. These are validated using experimental data from DLD1 spheroids at different stages of growth. A relatively constant experimentally derived diffusion limit of 232 ± 22 μm and an O 2 consumption rate of 7.29 ± 1.4 × 10 −7 m 3 kg −1 s −1 for the spheroids studied was measured, in agreement with laboratory measurements.